BOSTON (FRONTLINE MEDICAL NEWS) – Further parsing of data from the SCALE clinical trials reinforces the finding that an investigational dose of liraglutide, combined with diet and exercise, is linked with more weight loss in obese diabetic and nondiabetic adults than diet and exercise alone, albeit with significant GI adverse effects.
Among patients who completed the 56-week SCALE Obesity and Prediabetes trial, obese and prediabetic adults treated with an investigational 3-mg injectable daily dose of liraglutide plus calorie restriction and exercise lost a mean of 9.2% of their body weight, compared with 3.5% for patients who injected themselves with placebo and also dieted and exercised.
“Liraglutide 3 mg, in obese patients with prediabetes and without prediabetes, gave significantly more weight loss than in the placebo group, and it was independent of whether or not patients had prediabetes, or their body mass index,” Dr. Frank Greenway of the Pennington Biomedical Research Center in Baton Rouge, La., said at Obesity Week 2014, presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.
Patients with a baseline BMI of up to 29.9 kg/m2 lost an average of 7.5% of body weight, those with a BMI of 30-34.9 lost 8.3%, those with a BMI of 35-39.9% dropped 9.3% on average, and those with BMIs of 40 or over shed 7.4%. In each category, the difference between the liraglutide and placebo groups was significant (P < .0001).
Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue approved in the United States as a 1.2-mg and 1.8-mg daily subcutaneous injection as an adjunct to diet and exercise in patients with type 2 diabetes. It is not recommended as first-line therapy for patients with diabetes that is not adequately controlled with diet and exercise. On the basis of the results of the SCALE trials and others, advisers to the Food and Drug Administration in September recommended that the 3-mg dose be approved for weight management in adults. At press time, no decision on the application by the manufacturer, Novo Nordisk, had been made by the FDA.
The SCALE trial enrolled 3,731 patients and randomized them on a 2:1 basis to liraglutide (2,487) or placebo (1,244).
GI adverse events common
The most common adverse event with liraglutide over the course of the study was nausea, which occurred in 40% of patients who injected the drug, compared with 15% of patients who injected a placebo. Diarrhea occurred in 21% and 9%., respectively, and vomiting occurred in 16% and 4%.
Despite these adverse events, which tended to peak by the 6th to 8th week of the study, more patients in the placebo group dropped out of the study (28.1% vs. 35.6%), said Dr. Ken Fujioka of the department of nutrition and metabolic research at the Scripps Clinic in La Jolla, Calif.
“This is a high rate of nausea,” Dr. Fujioka said. He noted that the trial protocol required an upward dose titration that could not be reversed without causing the patient to exit the study, which could partially explain the high rate of gastrointestinal distress seen with the drug.
Dr. Fujioka reported health-related quality of life data from the trial, based on scores in the Short Form–36 (SF-36) and Impact of Weight on Quality of Life–Lite (IWQoL-Lite) questionnaires, which showed better, albeit modest, gains over baselines in patients on liraglutide compared with placebo.
Liraglutide in diabetes patients
Dr. Robert F. Kushner of Northwestern University, Chicago, reported results from a separate trial from the SCALE clinical trial series, SCALE-Diabetes , looking at health-related quality of life in 846 overweight or obese patients with type 2 diabetes treated with liraglutide at the investigational 3-mg dose, the approved 1.8-mg dose, or placebo. All patients also engaged in calorie restriction and exercise.
At week 56, the mean body weight percentage lost from baseline was 5.9% in the 3-mg group, 4.6% in the 1.8 mg group, and 2% in the placebo group.
Compared with placebo, there was a significantly better mean total improvement in the IWQoL-Lite score with the 3-mg dose but not with the 1.8-mg dose. Gastrointestinal adverse events also were common in this trial, with nausea occurring in 33% on the 3-mg dose, 31% on the 1.8-mg dose, and 14% of patients on placebo. Diarrhea occurred in 26%, 18%, and 13%, respectively, and constipation in 16%, 10%, and 6%.
“The nausea that is seen in this trial primarily occurs from the first 12-16 weeks and then settles down, and there is not that much difference thereafter,” Dr. Kushner said.
Too expensive?
An obesity researcher who was not involved in the study noted that liraglutide is not yet reimbursed for weight loss, and has an adverse event profile that may discourage some patients from remaining on the drug.
“I think that for those people who can tolerate the medication and who can afford it, it’s better than placebo. If you can have access to medication it’s great, but a lot of people are not able to stick to it for any duration of time, and that’s the downside of it. If you don’t stick to it, the weight comes back,” Dr. Ranjan Sudan, a surgeon at Duke University, Durham, N.C., and chair of the ASMBS Research Committee, said in an interview.
“If this medication, for instance, could show that down the road it prevented or prolonged the onset of diabetes, that would be a whole different thing, and there may be some justification for its use. But for the moment, being primarily for weight loss purposes and not to treat comorbidities makes it a little bit of a hard sell,” he said.
If approved, liraglutide 3 mg will be marketed as Saxenda. Liraglutide 1.8 mg was approved in 2010 and is marketed as Victoza.
The studies were supported by Novo Nordisk. Dr. Greenway and Dr. Kushner disclosed serving on the company’s advisory board. Dr. Fujioka disclosed receiving research support and consulting with the company.
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